The order picking process is often the single largest expense in a distribution centre (DC). The DC considered in this paper uses a picking line configuration to perform order picking. The number of pickers in a picking line, and the initial arrangement of stock-keeping units (SKUs), are two important factors that affect the total completion time of the picking lines. In this paper, the picking line configuration is simulated with an agent-based approach to describe the behaviour of an individual picker. The simulation is then used to analyse the effect of the number of pickers and the SKU arrangement. Verification and validation of this model shows that the model represents the real-world picking line to a satisfactory degree. Marginal analysis (MA) was chosen to determine a ‘good’ number of pickers by means of the simulation model. A look-up table is presented to provide decision support for the choice of a ‘good’ number of pickers to improve completion times of the picking line, for the properties of a specific picking line. The initial SKU arrangement on a picking line is shown to be a factor that can affect the level of picker congestion and the total completion time. The greedy ranking and partitioning (GRP) and organ pipe arrangement (OPA) techniques from the literature, as well as the historical SKU arrangements used by the retailer under consideration, were compared with the proposed classroom discipline heuristic (CDH) for SKU arrangement. It was found that the CDH provides an more even spread of SKUs that are picked most frequently, thus decreasing congestion and total completion time.